The American Cancer Society estimates the lifetime risk that an individual will develop cancer is 1 in 2 for men and 1 in 3 for women. The development of cancer, while still not completely understood, can be enhanced as a result of a variety of risk factors. For example, exposure to environmental factors (e.g., tobacco smoke) might trigger modifications in certain genes, thereby initiating cancer development. Alternatively, these genetic modifications may not require an exposure to environmental factors to become abnormal. Indeed, certain mutations (e.g., deletions, substitutions, etc.) can be inherited from generation to generation, thereby imparting an individual with a genetic predisposition to develop cancer.
Currently, the survival rates for many cancers are on the rise. One reason for this success is improvement in the detection of cancer at a stage at which treatment can be effective. Indeed, it has been noted that one of the most effective means to survive cancer is to detect its presence as early as possible. According to the American Cancer Society, the relative survival rate for many cancers would increase by about 15% if individuals participated in regular cancer screenings. Therefore, it is becoming increasingly useful to develop novel diagnostic tools to detect the cancer either before it develops or at an as early stage of development as possible.
One popular way of detecting cancer early is to analyze the genetic makeup of an individual to detect the presence or expression levels of a marker gene(s) related to the cancer. For example, there are various diagnostic methods that analyze a certain gene or a pattern of genes to detect cancers of the breast, tongue, mouth, colon, rectum, cervix, prostate, testis, and skin. Recently, measuring the level of expression of semenogelin has been found to be useful in the detection of prostate cancer.
Semenogelin is known to be the predominant protein in human semen. Normally, it is synthesized by the secretory epithelium of the seminal vesicles as a 461 amino acid precursor protein. Following cleavage of a predominantly hydrophobic signal peptide, the secreted protein contains 439 amino acid residues. Semenogelins I and II (hereinafter referred to as “SgI” and “SgII,” respectively) are two separate gene products resulting from the expression of semenogelin and are normally responsible for the gel formation in semen. SgI is a single-chain, non-glycosylated protein of 439 amino acids, whereas SgII contains 559 amino acids (Lilja et al., Proc. Natl. Acad. Sci. USA. 89 (10): 4559-4563 1992). Degradation of SgI and SgII is due to the proteolytic action of prostate-specific antigen (PSA), which also has been shown to be helpful in diagnosing prostate cancer.
While semenogelin has been detected in human semen, histological analyses have failed to detect semenogelin expression in any normal human tissue other than seminal vesicle epithelium and epidymis (Herr et al., Biol Reprod. 40: 333-342 (1989); Evans et al., Anat Rec. 214: 372-377 (1986); and Bjartell et al., J Androl. 17: 17-26 (1996). It has also been shown that a decrease in expression of semenogelin mRNA, as detected by RT-PCR, is indicative of prostate cancer (see, e.g., U.S. Pat. No. 5,972,615).
A need remains for additional ways to diagnose, prognosticate, and treat cancer. The invention provides such methods. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.